Extended Data Fig. 9: Performance of refined brain and organismal aging clocks with reduced number of proteins and their association with diseases and mortality.
From: Organ-specific proteomic aging clocks predict disease and longevity across diverse populations
a, RFE using SHAP values for brain and organismal aging clocks. Models were fitted iteratively using 5-fold cross-validation starting from full protein panels (230 for organismal aging and 70 for brain aging) down to a single protein. At each step, the protein with the smallest absolute mean SHAP value across folds was removed. The R2 for explained variance in chronological age was reported as the average across the five folds. Refined brain clocks with 10 proteins and organismal clocks with 20 proteins were ultimately identified. SHAP values for the refined protein panel are shown. b, Comparison of the predictive performance for chronological age between the full and refined versions of the brain/organismal aging clocks across cohorts. The orange bar denotes the percentage of feature reduction. c-e, Comparison of the association of the full versus refined versions of aging clocks with diseases and mortality in the UKB (n = 43,616), CKB (n = 3,977), and NHS (n = 774). Squares represent HRs and error bars the corresponding 95% CIs. Cox regression models were adjusted for age, sex, ethnicity, Townsend deprivation index, smoking, physical activity level, and recruitment center in UKB; for age, sex, ethnicity, education, study region, smoking, and physical activity in CKB; and for age, ethnicity, neighborhood socioeconomic status, smoking, and physical activity in NHS.
